2007 Fiscal Year Final Research Report Summary
Transcription factor networks in blood vessel-metabolic system crosstalk and metabolic syndrome
| Project/Area Number |
18390230
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MANABE Ichiro The University of Tokyo, Graduate School of Medicine, Project Lecturer (70359628)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Ryozo The University of Tokyo, Hospital, Professor (60207975)
NISHIMURA Go The University of Tokyo, Hospital, Intern Doctor (20422305)
FUJIU Katsuhito The University of Tokyo, Hospital, Research Associate (30422306)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Cardiovascular disease / Diabetes mellitus / Translational research / Atherosclerosis / Metabolic syndrome / Transcriptional regulation / KLF5 |
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| Research Abstract |
Obesity and metabolic syndrome are increasingly recognized as major risk factors for cardiovascular disease. In this project we analyzed the roles played by Kruppel-like transcription factor 5 (KLF5) in metabolic syndrome and cardiovascular disease. KLF5 heterozygous knockout (KLF5^<+/->) mice were resistant to high-fat-induced obesity, hypercholesterolemia, glucose intolerance and hepatic steatosis, despite consuming more food than wild-type mice. This may in part reflect their increased systemic O_2 consumption, indicating enhanced energy expenditure. Expression of the genes involved in lipid oxidation and energy uncoupling was upregulated in the soleus muscles of KLF5^<+/-> mice and in C2Cl2 myotubes in which KLF5 was knocked down. We demonstrated that KLF5 is a crucial regulator of energy metabolism. KLF5 acts with PPARδ to play a central role in transcriptional regulatory programs governing expression of genes related to fatty acid catabolism. KLF5 interacts with RAR in smooth muscle cells and the differences in interacting partners in different tissues appear to determine tissue-specific functions of KLF5.
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[Journal Article] In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue2008
Author(s)
Nishimura S, Manabe I, Nagasaki M, Seo K, Yamashita H, Hosoya Y, Ohsugi M, Tobe K, Kadowaki T, Nagai R, Sugiura S.
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Journal Title
J Clin Invest 118(2)
Pages: 710-721
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels2007
Author(s)
Nishimura S, Manabe I, Nagasaki M, Hosoya Y, Yamashita H, Fujita H, Ohsugi M, Tobe K, Kadowaki T, Nagai R, Sugiura S.
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Journal Title
Diabetes 56(6)
Pages: 1517-1526
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] deltaEF1 mediates TGF-beta signaling in vascular smooth muscle cell differentiation2006
Author(s)
Nishimura G, Manabe I, Tsushima K, Fujiu K, Oishi Y, Imai Y, Maemura K, Miyagishi M, Higashi Y, Kondoh H, Nagai R.
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Journal Title
Dev Cell 11(1)
Pages: 93-104
Description
「研究成果報告書概要(欧文)」より
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